ABSTRACT
Objective: To investigate the association between the genetic polymorphism of ABCB1 C3435T and plasma concentration and adverse reactions of high-dose methotrexate(HD-MTX) chemotherapy in children with acute lymphoblastic leukemia(ALL).Methods: A total of 70 peripheral blood samples were obtained from the children with acute lymphoblastic leukemia for extracting genome DNA.The genetic polymorphism of ABCB1 C3435T locus was examined by using PCR technology and direct sequencing;enzyme-amplified immunoassay (EMIT) was employed to determine the plasma concentration of MTX in 48 h;the clinical data of patients were collected during the HD-MTX chemotherapy, the adverse reactions were statistically analyzed.The association between ABCB1 C3435T genotypes and MTX plasma concentration and adverse reactions were investigated.Results: Genetic polymorphism existed at the SNP of ABCB1 C3435T.At the SNP of ABCB1 C3435T, the percentage of CC, CT and TT genotype in the children with ALL was 31.43%, 47.14% and 21.43%, respectively.The order of C/D ratio of MTX from low to high was CC, CT and TT genotypes, there was a significant association between the gene polymorphism and the C/D ratio of MTX (P<0.05);the order of incidence of oral mucosa damage from low to high was CC, CT and TT genotypes, there was a significant association between the gene polymorphism and oral mucosa damage (P<0.05);the order of incidence of hepatotoxicity from low to high were CC, CT and TT genotypes, the gene polymorphism and hepatotoxicity had a significant association (P<0.05).Conclusion: ABCB1 C3435T genetic polymorphism and C/D ratio of MTX, gastrointestinal side effects and hepatotoxicity after HD-MTX chemotherapy in the children with ALL exhibit significant association.
ABSTRACT
Objective:To study the antihypertensive effect of the extract from compound Prunella vulgaris L. in spontaneous hy-pertension(SH)rats. Methods:Forty SH rats were randomly divided into the model group,high,middle and low dose groups of ex-tract from vompound Prunella vulgaris L. ,the compound kendir leaves tablets Ⅰ group with 8 ones in each. Non-invasive blood pres-sure measurement was used to detect the SBP and DBP of the SHR rats. Then the serum NO,AngⅡ ,ET-1 and ANP content were measured after the eight-week treatment. The pathological changes were observed after kidney HE staining in the SH rats. Results:Compared with that in the model group,the blood pressure in high-dose treatment group,middle-dose treatment group and the positive model group was significantly decreased(P < 0. 05). The AngⅡ and ET-1 levels in high-dose treatment group,middle-dose treatment group and the positive model group were decreased(P < 0. 01),and NO and ANP contents in serum were significantly increased when compared with those in the model group(P < 0. 01). The pathological examination showed that the pathological changes in the model group were faster than those in all the drug-treatment groups,the pathological changes included glomerular and renal tubular atrophy, glomerular vascular wall thickening and renal tubular epithelial cell degeneration or necrosis. Conclusion:The extract from compound Prunella vulgaris L. can reduce blood pressure of SH rats. The mechanism may be associated with the level reduction of AngII and ET-1 and content elevation of NO and ANP.
ABSTRACT
Objective:To investigate the vasorelaxant effect of active fraction from compound Prunella vulgaris L. ( AFCP) on the i-solated thoracic aorta of rats and underlying mechanism. Methods:The study was performed with the tension experiment of the isolate rat thoracic aorta. The changes of vascular ring tension were measured by biological signal acquisition and analysis system, and the vasodila-tor effect of AFCP was observed. Results:AFCP(100-500μg·ml-1)could induce significant relaxation in aorta rings pre-contracted by phenylephrine (PE,1 μmol·L-1), and the relaxation effect was significant(75% ±8%) in endothelium-intact aortic and endothelium-denuded aortic. The vasodilatation effect of AFCP was not significantly affected by nitric oxide synthase ( NOS) inhibitor NG-nitro-L-argi-nine( L-NNA) , guanylate cyclase inhibitor MB,potassium channel blocker TEA and glibenclamide. In Ca2+-free bath solutions, AFCP (300 μg·ml-1 ) could shift downward dose-response curve of CaCl2 and significantly reduce the maximum contraction amplitude of PE. Conclusion:AFCP can relax rat aorta rings in a dose-dependent manner, which is endothelium-independent. The mechanism may be re-lated to the inhibition of intracellular calcium release and extracellular calcium flow, and has nothing to do with NO pathway, prostacyclin generation and calcium-activated potassium channels.